Diphtheria toxin or its mutant such as CRM197 has an activity to inhibit the binding of HB-EGF to EGF receptor by binding to an EGF-like domain in soluble and non-soluble (membrane-anchored) HB-EGF. A receptor binding domain in diphtheria toxin is involved in this binding.
Various studies have been performed on anti-cancer effects of CRM197. For example, it is described in Patent Document 1 that CRM197 is effective for a breast cancer, an ovarian cancer, a prostate cancer and a thyroid cancer. It is disclosed in Non-patent Literature 1 that when CRM197 was administered to patients with cancer having the metastasis, complete responses were observed in the breast cancer and a neuroblastoma, but the cancer progressed in cases of a non-small cell lung cancer, the colon cancer and the bladder cancer.
No effective anticancer agent is available for the peritoneal metastasis of the stomach cancer and the pancreatic cancer, whose prognosis is known to be poor. No effect of diphtheria toxin or its mutant such as CRM197 on these cancers have been known.
Patent Document 1: JP 2004-155776-A
Non-patent Literature 1: S. Buzzi, et al. Cancer Immunol. Immunother. (2004) 53: 1041-1048